3-DIMENSIONAL NMR OF DIHYDROFRLATE REDUCTASE

这项研究工作的目标是加深对 溶液中重要的生物分子以阐明其作用机制 行动的一部分。在这个项目中，提出了一项关于 二氢叶酸还原酶的结构和动力学性质 来自E.Coli。这是一种参与代谢控制的重要酶。 以及生物合成中重要前体的合成。因为这个原因， 它的广泛分布一直是药物设计的目标。几个 抗二氢叶酸还原酶药物已被用作抗菌药物 和抗癌剂。这里的工作将探索药物-酶 相互作用，以改进对此的抑制剂的合理设计 酵素。核磁共振是治疗癌症最有效的技术 这样的研究，但这种蛋白质是对溶液核磁共振的挑战，因为 它的大小。同位素标记的三维核磁共振新技术 蛋白质在溶液构象中表现出很大的前景 分析。这笔拨款将支持一所领先的 正在开发和应用新方法的实验室 促进关于这种酶的方法学的使用。

The goal of the research effort is to develop an understanding of biologically important molecules in solution to elucidate their mechanism of action. In this project an investigation is proposed of the structural and dynamic properties of the enzyme dihydrofolate reductase from E. coli. This is an important enzyme involved in metabolic control and synthesis of important precursors in biosynthesis. For this reason, and its wide distribution it has been a target for drug design. Several anti-dihydrofolate reductase drugs are already in use as antibacterial and anticancer agents. The work here will explore the drug - enzyme interactions to improve the rational design of inhibitors for this enzyme. Nuclear magnetic resonance is the most effective technique for such studies, but this protein is a challenge to solution NMR because of its size. New 3-dimensional NMR techniques with isotopically labeled protein show a great deal of promise in the solution conformational analysis. This grant will support research at one of the leading laboratories where the new approaches are being developed and applied to facilitate the use of the methodologies on this enzyme.